Integrated Analysis of Gene Expression Differences in Twins Discordant for Disease and Binary Phenotypes.
Integrated Analysis of Gene Expression Differences in Twins Discordant for Disease and Binary Phenotypes.
复制标题
疾病和二元表型不一致的双胞胎基因表达差异的综合分析。
DOI：
10.1038/s41598-017-18585-3
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发表时间：
2018
影响因子：
4.6
通讯作者：
Patel,ChiragJ
中科院分区：
文献类型：
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作者：
Tangirala,Sivateja;Patel,ChiragJ
虽然基因和环境都对表型有贡献，但破译环境对表型的贡献是一个挑战。此外，阐明不同表型如何共享相似的环境病因也具有挑战性。识别环境影响的一种方法是通过不一致的同卵双生 (MZ) 研究设计。在这里，我们评估了同卵双胞胎（受影响与未受影响）的七种表型的差异基因表达，包括慢性疲劳综合征、肥胖、溃疡性结肠炎、重度抑郁症、间歇性过敏性鼻炎、体力活动和智商，并分别比较了七种表型中差异表达的基因谱。其次，我们对每个基因进行了荟萃分析，以确定七种表型之间基因表达特征的共性和差异。在我们的综合分析中，我们发现各个表型可能存在共同的基因表达特征（效应量较小）；然而，差异表达基因的表型之间的差异更为突出。因此，定义表型中常见的环境诱导途径仍然难以捉摸。我们通过为研究人员提供一个新的数据库（DiscTwinExprDB：http://apps.chiragjpgroup.org/disctwinexprdb/）来研究基因表达的非基因型影响，从而使我们的工作变得容易理解。
While both genes and environment contribute to phenotype, deciphering environmental contributions to phenotype is a challenge. Furthermore, elucidating how different phenotypes may share similar environmental etiologies also is challenging. One way to identify environmental influences is through a discordant monozygotic (MZ) twin study design. Here, we assessed differential gene expression in MZ discordant twin pairs (affected vs. non-affected) for seven phenotypes, including chronic fatigue syndrome, obesity, ulcerative colitis, major depressive disorder, intermittent allergic rhinitis, physical activity, and intelligence quotient, comparing the spectrum of genes differentially expressed across seven phenotypes individually. Second, we performed meta-analysis for each gene to identify commonalities and differences in gene expression signatures between the seven phenotypes. In our integrative analyses, we found that there may be a common gene expression signature (with small effect sizes) across the phenotypes; however, differences between phenotypes with respect to differentially expressed genes were more prominently featured. Therefore, defining common environmentally induced pathways in phenotypes remains elusive. We make our work accessible by providing a new database (DiscTwinExprDB:http://apps.chiragjpgroup.org/disctwinexprdb/) for investigators to study non-genotypic influence on gene expression.